Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction

Yukio Shimasaki, Hirofumi Yasue, Michihiro Yoshimura, Masafumi Nakayama, Kiyotaka Kugiyama, Hisao Ogawa, Eisaku Harada, Takenobu Masuda, Wasaku Koyama, Yoshihiko Saito, Yoshihiro Miyamoto, Yoshihiro Ogawa, Kazuwa Nakao

Research output: Contribution to journalArticle

318 Citations (Scopus)

Abstract

Objectives. We examined the possible association between the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and myocardial infarction (MI). Background. Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone. Recently, we reported that a missense Glu298Asp variant in exon 7 of the eNOS gene is a possible genetic factor involved in the pathogenesis of coronary spasm. Endothelium- derived NO also has vasoprotective effects by suppressing platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation. Methods. We screened 285 patients with an MI and 607 control subjects in Kumamoto Prefecture, Japan. Genotypes were determined by polymerase chain reaction-restriction fragment-length polymorphism analysis. Results. The frequency of the missense Glu298Asp variant was significantly higher in the MI group than in the control group (21.1% vs. 13.3%, p = 0.003, odds ratio 1.73 for the dominant effect of the eNOS T allele). Multiple logistic regression analysis showed that the missense Glu298Asp variant was an independent risk factor for MI, as was diabetes mellitus, hypertension, cigarette smoking, hypercholesterolemia and body mass index. Conclusions. There was a significant association of the missense Glu298Asp variant of the eNOS gene with MI. This marker-disease association may be due to the impaired effects of NO on the cardiovascular system: dysregulation of vascular tone, platelet aggregation and leukocyte adhesion and smooth muscle cell proliferation, all of which promote coronary atherosclerosis and thrombosis.

Original languageEnglish
Pages (from-to)1506-1510
Number of pages5
JournalJournal of the American College of Cardiology
Volume31
Issue number7
DOIs
Publication statusPublished - Jun 1 1998

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Nitric Oxide Synthase Type III
Myocardial Infarction
Nitric Oxide
Genes
Platelet Aggregation
Smooth Muscle Myocytes
Blood Vessels
Leukocytes
Cell Proliferation
Coronary Thrombosis
Spasm
Cardiovascular System
Hypercholesterolemia
Restriction Fragment Length Polymorphisms
Coronary Artery Disease
Exons
Diabetes Mellitus
Japan
Body Mass Index
Logistic Models

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction. / Shimasaki, Yukio; Yasue, Hirofumi; Yoshimura, Michihiro; Nakayama, Masafumi; Kugiyama, Kiyotaka; Ogawa, Hisao; Harada, Eisaku; Masuda, Takenobu; Koyama, Wasaku; Saito, Yoshihiko; Miyamoto, Yoshihiro; Ogawa, Yoshihiro; Nakao, Kazuwa.

In: Journal of the American College of Cardiology, Vol. 31, No. 7, 01.06.1998, p. 1506-1510.

Research output: Contribution to journalArticle

Shimasaki, Y, Yasue, H, Yoshimura, M, Nakayama, M, Kugiyama, K, Ogawa, H, Harada, E, Masuda, T, Koyama, W, Saito, Y, Miyamoto, Y, Ogawa, Y & Nakao, K 1998, 'Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction', Journal of the American College of Cardiology, vol. 31, no. 7, pp. 1506-1510. https://doi.org/10.1016/S0735-1097(98)00167-3
Shimasaki, Yukio ; Yasue, Hirofumi ; Yoshimura, Michihiro ; Nakayama, Masafumi ; Kugiyama, Kiyotaka ; Ogawa, Hisao ; Harada, Eisaku ; Masuda, Takenobu ; Koyama, Wasaku ; Saito, Yoshihiko ; Miyamoto, Yoshihiro ; Ogawa, Yoshihiro ; Nakao, Kazuwa. / Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction. In: Journal of the American College of Cardiology. 1998 ; Vol. 31, No. 7. pp. 1506-1510.
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abstract = "Objectives. We examined the possible association between the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and myocardial infarction (MI). Background. Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone. Recently, we reported that a missense Glu298Asp variant in exon 7 of the eNOS gene is a possible genetic factor involved in the pathogenesis of coronary spasm. Endothelium- derived NO also has vasoprotective effects by suppressing platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation. Methods. We screened 285 patients with an MI and 607 control subjects in Kumamoto Prefecture, Japan. Genotypes were determined by polymerase chain reaction-restriction fragment-length polymorphism analysis. Results. The frequency of the missense Glu298Asp variant was significantly higher in the MI group than in the control group (21.1{\%} vs. 13.3{\%}, p = 0.003, odds ratio 1.73 for the dominant effect of the eNOS T allele). Multiple logistic regression analysis showed that the missense Glu298Asp variant was an independent risk factor for MI, as was diabetes mellitus, hypertension, cigarette smoking, hypercholesterolemia and body mass index. Conclusions. There was a significant association of the missense Glu298Asp variant of the eNOS gene with MI. This marker-disease association may be due to the impaired effects of NO on the cardiovascular system: dysregulation of vascular tone, platelet aggregation and leukocyte adhesion and smooth muscle cell proliferation, all of which promote coronary atherosclerosis and thrombosis.",
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AU - Yasue, Hirofumi

AU - Yoshimura, Michihiro

AU - Nakayama, Masafumi

AU - Kugiyama, Kiyotaka

AU - Ogawa, Hisao

AU - Harada, Eisaku

AU - Masuda, Takenobu

AU - Koyama, Wasaku

AU - Saito, Yoshihiko

AU - Miyamoto, Yoshihiro

AU - Ogawa, Yoshihiro

AU - Nakao, Kazuwa

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N2 - Objectives. We examined the possible association between the missense Glu298Asp variant of the endothelial nitric oxide synthase (eNOS) gene and myocardial infarction (MI). Background. Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone. Recently, we reported that a missense Glu298Asp variant in exon 7 of the eNOS gene is a possible genetic factor involved in the pathogenesis of coronary spasm. Endothelium- derived NO also has vasoprotective effects by suppressing platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation. Methods. We screened 285 patients with an MI and 607 control subjects in Kumamoto Prefecture, Japan. Genotypes were determined by polymerase chain reaction-restriction fragment-length polymorphism analysis. Results. The frequency of the missense Glu298Asp variant was significantly higher in the MI group than in the control group (21.1% vs. 13.3%, p = 0.003, odds ratio 1.73 for the dominant effect of the eNOS T allele). Multiple logistic regression analysis showed that the missense Glu298Asp variant was an independent risk factor for MI, as was diabetes mellitus, hypertension, cigarette smoking, hypercholesterolemia and body mass index. Conclusions. There was a significant association of the missense Glu298Asp variant of the eNOS gene with MI. This marker-disease association may be due to the impaired effects of NO on the cardiovascular system: dysregulation of vascular tone, platelet aggregation and leukocyte adhesion and smooth muscle cell proliferation, all of which promote coronary atherosclerosis and thrombosis.

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